IL181247A - Use of 5,5-diphenyl barbituric acid in the preparation of an oral dosage form to improve the bioavailability of 5,5-diphenyl barbituric acid - Google Patents

Use of 5,5-diphenyl barbituric acid in the preparation of an oral dosage form to improve the bioavailability of 5,5-diphenyl barbituric acid

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Publication number
IL181247A
IL181247A IL181247A IL18124707A IL181247A IL 181247 A IL181247 A IL 181247A IL 181247 A IL181247 A IL 181247A IL 18124707 A IL18124707 A IL 18124707A IL 181247 A IL181247 A IL 181247A
Authority
IL
Israel
Prior art keywords
diphenyl
acid
barbituric acid
dosage form
sodium salt
Prior art date
Application number
IL181247A
Other versions
IL181247A0 (en
Original Assignee
Taro Pharma Ind
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Taro Pharma Ind filed Critical Taro Pharma Ind
Publication of IL181247A0 publication Critical patent/IL181247A0/en
Publication of IL181247A publication Critical patent/IL181247A/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
    • A61K31/515—Barbituric acids; Derivatives thereof, e.g. sodium pentobarbital
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/08—Antiepileptics; Anticonvulsants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/22—Anxiolytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A61P39/04—Chelating agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/60—Three or more oxygen or sulfur atoms
    • C07D239/62—Barbituric acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/60—Three or more oxygen or sulfur atoms
    • C07D239/62—Barbituric acids
    • C07D239/64—Salts of organic bases; Organic double compounds

Abstract

The present invention relates to a composition and a method of delivering a barbituric acid derivative to the central nervous system of a mammal in need of treatment for neurological conditions. In particular, the present invention relates to a method of administering an oral dosage form of a sodium salt of 5,5-diphenyl barburtic acid to enhance the bioavailability of 5,5-diphenyl barbituric acid and brain delivery of same.

Claims (49)

What is claimed is:
1. Use of an isolated sodium salt of 5,5-diphenyl barbituric acid in the preparation of an oral dosage form to improve the bioavailability of 5,5-diphenyl barbituric acid in a mammal in need of anti-convulsant treatment, wherein the oral dosage form is a solid or suspension.
2. The use of claim 1, wherein the isolated salt of 5,5-diphenyl barbituric acid is substantially pure.
3. The use of claim 1, wherein the isolated salt of 5,5-diphenyl barbituric acid is at least about 90% pure.
4. The use of claim 1 , wherein the oral dosage form provides an AUC0-48 of 5,5-diphenyl barbituric acid of at least 800 μg*hr/mL.
5. The use of claim 1, wherein the oral dosage form provides ah AUC0-48 of 5,5-diphenyl barbituric acid of at least 1,200 μg*hr /mL.
6. The use of claim 1, wherein the oral dosage form provides an AUCo-48 of 5,5-diphenyl barbituric acid of at least 1,500 \ig*hr /mL.
7. The use of claim 1, wherein the oral dosage form provides a Cmax of 5,5-diphenyl barbituric acid of at least 50 μg /mL.
8. The use of claim 1, wherein the oral dosage form provides a Cmax of 5,5-diphenyl barbituric acid of at least 75 μg /mL.
9. The use of claim 1, wherein the oral dosage form provides a Cmax of 5,5-diphenyl barbituric acid of at least 100 μg /mL. 181247/2
10. The use of claim 1, wherein the oral dosage form provides an AUCo-48 of 5,5-diphenyl barbituric acid that is at least about 1.5 times greater than that provided by oral administration of the same amount of a free acid form of 5,5-diphenyl barbituric acid.
11. 1 1. The use of claim 1 , wherein the oral dosage form provides 'an AUCo-48 of 5,5-diphenyl barbituric acid that is at least about 2 times greater than that provided by oral administration of the same amount of a free acid form of 5,5-diphenyl barbituric acid.
12. The use of claim 1, wherein the oral dosage form provides an AUC0.48 of 5,5-diphenyl barbituric acid that is at least about 2.5 times greater than that provided by oral administration of the same amount of a free acid form of 5,5-diphenyl barbituric acid.
13. The use of claim 1, wherein the oral dosage form provides an AUQ S of 5,5-diphenyl barbituric acid that is at least about 3 times greater than that provided by oral administration of the same amount of a free acid form of 5,5-diphenyl barbituric acid.
14. The use of claim 1, wherein the oral dosage form provides an AUC0-48 5,5-diphenyl barbituric acid that is at least about 3.5 times greater than that provided by oral administration of the same amount of a free acid form of 5,5-diphenyl barbituric acid.
15. The use of claim 1 , wherein the oral dosage form provides a Cmax of 5,5-diphenyl barbituric acid that is at least about 1.5 times greater than that provided by oral administration of the same amount of a free acid form of 5,5-diphenyl barbituric acid.
16. The use of claim 1, wherein the oral dosage form provides a Cmax of 5,5-diphenyl barbituric acid that is at least about 2 times greater than that provided by oral administration of the same amount of a free acid form of 5,5-diphenyl barbituric acid.
17. The use of claim 1, wherein the oral dosage form provides a Cmax of 5,5-diphenyl barbituric acid that is at least about 2.5 times greater than that provided by oral administration of the same amount of a free acid form of 5,5-diphenyl barbituric acid. 181247/2
18. The use of claim 1, wherein the salt of 5,5-diphenylbarbituric acid is in a sufficient amount to provide a brain concentration of 5,5-diphenylbarbituric acid that is at least about 1.5 times greater than that provided by oral administration of the same amount of a free acid form of 5,5-diphenylbarbituric acid.
19. The use of claim 1, wherein the salt of 5,5-diphenylbarbituric acid is in a sufficient amount to provide a brain concentration of 5,5-diphenylbarbituric acid that is at least about 2 times greater than that provided by oral administration of the same amount of a free acid form of 5,5-diphenylbarbituric acid.
20. The use of claim 1, wherein the salt of 5,5-diphenylbarbituric acid is in a sufficient amount to provide a brain concentration of 5,5-diphenylbarbituric acid that is at least about 3 times greater than that provided by oral administration of the same amount of a free acid form of 5,5-diphenylbarbituric acid.
21. The use of claim 1, wherein the salt of 5,5-diphenylbarbituric acid is in a sufficient amount to provide a brain concentration of 5,5-diphenylbarbituric acid that is at least about 4 times greater than that provided by oral administration of the same amount of a free acid form of 5,5-diphenylbarbituric acid.
22. The use of claim 1, wherein the sodium salt of 5,5-diphenyl barbiturate provides a brain concentration of 5,5-diphenyl barbituric acid of at least about 20 μg/g at 24 hours after the administration.
23. The use of claim 1, wherein the sodium salt of 5,5-diphenyl barbiturate provides a brain concentration of 5,5-diphenyl barbituric acid of at least about 20 μg/g at 36 hours after the administration.
24. The use of claim 1, wherein the sodium salt of 5,5-diphenyl barbiturate provides a brain concentration of 5,5-diphenyl barbituric acid of at least about 8 μg/g at 48 hours after the administration. 181247/2
25. The use of claim 1, wherein the oral dosage form is a tablet, pill, capsule, caplet, powder, granule, suspension, gel or soft gel.
26. The use of claim 1, wherein the sodium salt of 5,5-diphenyl barbiturate is at a dosage from about 0.5 mg/kg to about 100 mg kg.
27. The use of claim 1, wherein the sodium salt of 5,5-diphenyl barbiturate is at a dosage from about 2 mg/kg to about 25 mg/kg.
28. The use of claim 1, wherein the sodium salt of 5,5-diphenyl barbiturate is at a dosage from about 3 mg/kg to about 15 mg/kg.
29. The use of claim 1, wherein the sodium salt of 5,5-diphenyl barbiturate is at a dosage of about 5 mg/kg to 10 mg/kg.
30. The use of claim 1, wherein the sodium salt of 5,5-diphenyl barbiturate is in the amount of from about 30 mg to about 3,000 mg per day.
31. The use of claim 1, wherein the sodium salt of 5,5-diphenyl barbiturate is in the amount of from 60 mg to about 1,500 mg per day.
32. The use of claim 1, wherein the sodium salt of 5,5-diphenyl barbiturate is in the amount of from 150 mg to about 900 mg per day.
33. The use of claim 1, wherein the sodium salt of 5,5-diphenyl barbiturate is in the amount of about 300 mg to about 600 mg per day.
34. The use of claim 1, wherein the mammal is a dog.
35. The use of claim 1, wherein the mammal is a human. 181247/2
36. Use of an isolated sodium salt of 5,5-diphenyl barbituric acid in the preparation of a medicament for the treatment of a mammal, wherein the medicament is solid oral dosage form.
37. The use of claim 36, wherein the sodium salt of 5,5-diphenyl barbiturate is at a dosage from about 0.5 mg/kg to about 100 mg/kg.
38. The use of claim 36, wherein the sodium salt of 5,5-diphenyl barbiturate is at a dosage from about 2 mg/kg to about 25 mg/kg.
39. The use of claim 36, wherein the sodium salt of 5,5-diphenyl barbiturate is at a dosage of about 5 mg/kg to 10 mg/kg.
40. The use of claim 36, wherein the solid dosage form is for once per day administration.
41. The use of claim 40, wherein the solid dosage form is for at least one week administration.
42. The use of claim 40, wherein the solid dosage form is for at least two weeks administration.
43. Use of an isolated salt of 5,5-diphenyl barbituric acid in the preparation of an oral dosage form for treatment of a mammal in need of anti-convulsant treatment, wherein the oral dosage form is a solid or a suspension, and the oral dosage form comprises isolated sodium salt of 5,5-diphenyl barbituric acid in an amount at least 30% less than the amount of 5,5-diphenyl barbituric acid required to achieve the same therapeutic blood level.
44. The use of claim 43, wherein the therapeutic blood level is an AUC0-l at least 800 μ *hr/mL. 181247/2
45. The use of claim 43, wherein the therapeutic blood level is a Cmax of at least 50 μg /mL.
46. The use of claim 1, wherein the sodium salt of 5,5-diphenyl barbiturate is at a dosage of about 50 mg kg to 150 mg/kg.
47. The use of claim 1, wherein the sodium salt of 5,5-diphenyl barbiturate is at a dosage of about 75 mg kg to 150 mg/kg.
48. The use of claim 36, wherein the sodium salt of 5,5-diphenyl barbiturate is at a dosage of about 50 mg/kg to 150 mg/kg.
49. The use of claim 36, wherein the sodium salt of 5,5-diphenyl barbiturate is at a dosage of about 75 mg/kg to 150 mg/kg. Respectfully submitted, 0 Osnat Bar-Peled, PhD IP Director Taro Pharmaceutical Industries 1/12 Mean Plasma Concentrations of MMMDPB and DPB After Single Oral Doses of MMMDPB in Beagle Dogs (30 mg/kg, n=8) Time (hr) 2/12 Mean Plasma Concentrations of MMMDPB and DPB After Single Oral Doses of NaMMMDPB in Beagle Dogs (30 mg/kg, n=8) 12 Time (hr) 3/12 Mean Plasma Concentrations of MMMOPB and DPB After Single intravenous Infusions of NaMMMDPB in Beagle Dogs (15 mg kg, T=15 min, n=8) Time (hr) 4/12 SVfeanRasnOO- centi^ of DPB in Beagte Dogs (75 mgfcg, ITF8) 12 18 24 3D 35 42 5/12 Mean Plasma Concentrations of DPB After Single Oral Doses of NaDPB in Beagle Dogs (75 mg/kg, n=8) Time (hr) 6/12 ft/lean Rasma Concentrations of DPB ter Single N Infusions of NaDPB in Beagle Oogs (75 mg/kg, T¼30 rrin, n≤4) 120 0 6 12 18 24 30 36 42 48 Time (hi) 7/12 8/12 Mean Plasma Concentrations of DPB After Single Oral Doses of NaDPB in Sprague-Dawley Rats (150 mg kg, n=18) Time (hr) 9/12 iNk=CPBin^¾gL©¾^^(15Dm^T^rrir π 8} Q. 0 6 12 18 24 3S 10/12 Mean Brain Concentrations of DPB After Single Oral Doses of DPB in Sprague-Dawley Rats (150 mg/kg, n=18) n 0 4 1 1) I I ■ I v ί I ι ] 0 6 12 18 24 30 36 42 48 Time (hr) 11/12 Mean Brain Concentrations of DPB After Single Oral Doses of NaDPB in Sprague-Dawley Rats (150 mg/kg, n=18) 18 24 Time (hr) 12/12 Mean Brain Concentrations of DPB After Single Intravenous Infusions of NaDPB in Sprague-Dawley Rats (150 mg/kg, T=30 rrin, n=18)
IL181247A 2004-08-10 2007-02-08 Use of 5,5-diphenyl barbituric acid in the preparation of an oral dosage form to improve the bioavailability of 5,5-diphenyl barbituric acid IL181247A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US60032704P 2004-08-10 2004-08-10
PCT/US2005/028380 WO2006026095A2 (en) 2004-08-10 2005-08-10 Composition and method for improved bioavailability and enhanced brain delivery of 5,5-diphenyl barbituric acid

Publications (2)

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IL181247A0 IL181247A0 (en) 2007-07-04
IL181247A true IL181247A (en) 2012-05-31

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EP (2) EP1625848A1 (en)
JP (2) JP2008509914A (en)
KR (2) KR20070074549A (en)
CN (2) CN101052403A (en)
AT (1) ATE510541T1 (en)
AU (1) AU2005280419B2 (en)
BR (1) BRPI0513337A (en)
CA (1) CA2576832C (en)
HK (1) HK1108313A1 (en)
IL (1) IL181247A (en)
MX (1) MX2007001655A (en)
NZ (1) NZ553653A (en)
SG (1) SG163500A1 (en)
WO (1) WO2006026095A2 (en)
ZA (1) ZA201106419B (en)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6756379B2 (en) 2001-07-26 2004-06-29 Taro Pharmaceutical Industries Ltd. Non-sedating barbiturate compounds as neuroprotective agents
US7683071B2 (en) 2000-07-26 2010-03-23 Taro Pharmaceuticals Industries Ltd. Composition and method for improved bioavailability and enhanced brain delivery of 5,5-diphenyl barbituric acid
JP4739760B2 (en) 2002-12-11 2011-08-03 タロー・ファーマシューティカル・インダストリーズ・リミテッド Method for treating movement disorders using barbituric acid derivatives
EP1625848A1 (en) * 2004-08-10 2006-02-15 Taro Pharmaceuticals North America, Inc. Composition and method for enhanced delivery of 5,5-diphenyl barbituric acid
CN102863579B (en) * 2012-09-14 2014-02-05 东南大学 Barbituric acid chelating resin and preparation method and application thereof
KR102162003B1 (en) 2014-04-14 2020-10-06 삼성전자주식회사 Method and device for controlling wireless network connection
KR101822417B1 (en) * 2017-06-14 2018-01-29 주식회사 청도제약 Means for determination of oxdative stress in human fluid

Family Cites Families (9)

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Publication number Priority date Publication date Assignee Title
US2119701A (en) * 1934-06-29 1938-06-07 Winthrop Chem Co Inc Alkoxyalkyl mercury nitrogen compounds
IL69722A (en) * 1983-09-14 1986-09-30 Taro Pharma Ind Oxopyrimidine derivatives and pharmaceutical compositions containing them
DE4433764A1 (en) * 1994-09-22 1996-03-28 Asta Medica Ag Dosage forms containing alpha-lipoic acid, solid salts of R-thioctic acid with improved release and bioavailability
US6093820A (en) * 1997-10-02 2000-07-25 Taro Pharmaceutical Industries Ltd. Method and reagents for N-alkylating ureides
US6756379B2 (en) * 2001-07-26 2004-06-29 Taro Pharmaceutical Industries Ltd. Non-sedating barbiturate compounds as neuroprotective agents
DE60132337T2 (en) * 2000-07-26 2009-02-12 Taro Pharmaceutical Industries Ltd. NON-SEDANT BARBITURATE COMPOUNDS AS NEUROPROTECTIVE ACTIVE SUBSTANCES
JP2005516052A (en) * 2002-01-30 2005-06-02 タロ ファーマシューティカル インダストリーズ リミテッド Non-sedating barbituric acid derivatives
JP4739760B2 (en) * 2002-12-11 2011-08-03 タロー・ファーマシューティカル・インダストリーズ・リミテッド Method for treating movement disorders using barbituric acid derivatives
EP1625848A1 (en) * 2004-08-10 2006-02-15 Taro Pharmaceuticals North America, Inc. Composition and method for enhanced delivery of 5,5-diphenyl barbituric acid

Also Published As

Publication number Publication date
JP2013177442A (en) 2013-09-09
CN102512422A (en) 2012-06-27
EP1781294A2 (en) 2007-05-09
ATE510541T1 (en) 2011-06-15
KR20120130256A (en) 2012-11-29
EP1781294B1 (en) 2011-05-25
CA2576832C (en) 2013-06-11
SG163500A1 (en) 2010-08-30
BRPI0513337A (en) 2008-05-06
KR20070074549A (en) 2007-07-12
ZA201106419B (en) 2012-05-30
WO2006026095A3 (en) 2007-02-01
AU2005280419B2 (en) 2010-09-23
HK1108313A1 (en) 2008-05-02
CN101052403A (en) 2007-10-10
EP1781294A4 (en) 2007-12-26
NZ553653A (en) 2010-06-25
AU2005280419A1 (en) 2006-03-09
MX2007001655A (en) 2007-04-23
EP1625848A1 (en) 2006-02-15
WO2006026095A2 (en) 2006-03-09
CA2576832A1 (en) 2006-03-09
IL181247A0 (en) 2007-07-04
JP2008509914A (en) 2008-04-03

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